Alterations of the Wnt/beta-catenin signaling pathway are positively associated with the development and progression of human
cancer, including
carcinoma of the prostate. To determine the role of activated Wnt/
beta-catenin signaling in mouse prostate
carcinogenesis, we created a mouse prostate
tumor model using
probasin-Cre-mediated deletion of Apc. Prostate
tumors induced by the deletion of Apc have elevated levels of
beta-catenin protein and are highly proliferative.
Tumor formation is fully penetrant and follows a consistent pattern of progression.
Hyperplasia is observed as early as 4.5 weeks of age, and
adenocarcinoma is observed by 7 months. Continued
tumor growth usually necessitated sacrifice between 12 and 15 months of age. Despite the high proliferation rate, we have not observed
metastasis of these
tumors to the lymph nodes or other organs. Surgical
castration of 6-week-old mice inhibited
tumor formation, and
castration of mice with more advanced
tumors resulted in the partial regression of specific prostate glands. However, significant areas of
carcinoma remained 2 months postcastration, suggesting that
tumors induced by Apc loss of function are capable of growth under conditions of
androgen depletion. We conclude that the prostate-specific deletion of Apc and the increased expression of
beta-catenin associated with prostate
carcinoma suggests a role for
beta-catenin in
prostate cancer and offers an appropriate animal model to investigate the interaction of Wnt signaling with other genetic and epigenetic signals in prostate
carcinogenesis.